Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

Zeggini, Eleftheria, Weedon, Michael N, Lindgren, Cecilia M, Frayling, Timothy M, Elliott, Katherine S, Lango, Hana, Timpson, Nicholas J, Perry, John R B, Rayner, Nigel W, Freathy, Rachel M, Barrett, Jeffrey C, Shields, Beverley, Morris, Andrew P, Ellard, Sian, Groves, Christopher J, Harries, Lorna W, Marchini, Jonathan L, Owen, Katharine R, Knight, Beatrice, Cardon, Lon R, Walker, Mark, Hitman, Graham A, Morris, Andrew D, Doney, Alex S F, McCarthy, Mark I, Hattersley, Andrew T, , Wellcome Trust Case Control Consortium and Forbes, Alastair (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science, 316 (5829). pp. 1336-41. ISSN 0036-8075

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Abstract

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.

Item Type: Article
Uncontrolled Keywords: adult,aged,case-control studies,chromosome mapping,diabetes mellitus, type 2,female,genes, p16,genetic predisposition to disease,genome, human,great britain,homeodomain proteins,humans,insulin-like growth factor binding proteins,introns,male,meta-analysis as topic,middle aged,oligonucleotide array sequence analysis,polymorphism, single nucleotide,transcription factors
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Nutrition
Depositing User: Pure Connector
Date Deposited: 06 Aug 2014 12:00
Last Modified: 21 Aug 2018 11:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/49677
DOI: 10.1126/science.1142364

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